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Yin, N. Early-onset Glaucoma. Encyclopedia. Available online: https://encyclopedia.pub/entry/5541 (accessed on 25 April 2024).
Yin N. Early-onset Glaucoma. Encyclopedia. Available at: https://encyclopedia.pub/entry/5541. Accessed April 25, 2024.
Yin, Nicole. "Early-onset Glaucoma" Encyclopedia, https://encyclopedia.pub/entry/5541 (accessed April 25, 2024).
Yin, N. (2020, December 25). Early-onset Glaucoma. In Encyclopedia. https://encyclopedia.pub/entry/5541
Yin, Nicole. "Early-onset Glaucoma." Encyclopedia. Web. 25 December, 2020.
Early-onset Glaucoma
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This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/condition/early-onset-glaucoma

Glaucoma is a group of eye disorders in which the optic nerves connecting the eyes and the brain are progressively damaged. This damage can lead to reduction in side (peripheral) vision and eventual blindness. Other signs and symptoms may include bulging eyes, excessive tearing, and abnormal sensitivity to light (photophobia). The term "early-onset glaucoma" may be used when the disorder appears before the age of 40.

genetic conditions

1. Introduction

In most people with glaucoma, the damage to the optic nerves is caused by increased pressure within the eyes (intraocular pressure). Intraocular pressure depends on a balance between fluid entering and leaving the eyes.

Usually glaucoma develops in older adults, in whom the risk of developing the disorder may be affected by a variety of medical conditions including high blood pressure (hypertension) and diabetes mellitus, as well as family history. The risk of early-onset glaucoma depends mainly on heredity.

Structural abnormalities that impede fluid drainage in the eye may be present at birth and usually become apparent during the first year of life. Such abnormalities may be part of a genetic disorder that affects many body systems, called a syndrome. If glaucoma appears before the age of 5 without other associated abnormalities, it is called primary congenital glaucoma.

Other individuals experience early onset of primary open-angle glaucoma, the most common adult form of glaucoma. If primary open-angle glaucoma develops during childhood or early adulthood, it is called juvenile open-angle glaucoma.

2. Frequency

Primary congenital glaucoma affects approximately 1 in 10,000 people. Its frequency is higher in the Middle East. Juvenile open-angle glaucoma affects about 1 in 50,000 people. Primary open-angle glaucoma is much more common after the age of 40, affecting about 1 percent of the population worldwide.

3. Causes

Approximately 10 percent to 33 percent of people with juvenile open-angle glaucoma have mutations in the MYOC gene. MYOC gene mutations have also been detected in some people with primary congenital glaucoma. The MYOC gene provides instructions for producing a protein called myocilin. Myocilin is found in certain structures of the eye, called the trabecular meshwork and the ciliary body, that regulate the intraocular pressure.

Researchers believe that myocilin functions together with other proteins as part of a protein complex. Mutations may alter the protein in such a way that the complex cannot be formed. Defective myocilin that is not incorporated into functional complexes may accumulate in the trabecular meshwork and ciliary body. The excess protein may prevent sufficient flow of fluid from the eye, resulting in increased intraocular pressure and causing the signs and symptoms of early-onset glaucoma.

Between 20 percent and 40 percent of people with primary congenital glaucoma have mutations in the CYP1B1 gene. CYP1B1 gene mutations have also been detected in some people with juvenile open-angle glaucoma. The CYP1B1 gene provides instructions for producing a form of the cytochrome P450 protein. Like myocilin, this protein is found in the trabecular meshwork, ciliary body, and other structures of the eye.

It is not well understood how defects in the CYP1B1 protein cause signs and symptoms of glaucoma. Recent studies suggest that the defects may interfere with the early development of the trabecular meshwork. In the clear covering of the eye (the cornea), the CYP1B1 protein may also be involved in a process that regulates the secretion of fluid inside the eye. If this fluid is produced in excess, the high intraocular pressure characteristic of glaucoma may develop.

The CYP1B1 protein may interact with myocilin. Individuals with mutations in both the MYOC and CYP1B1 genes may develop glaucoma at an earlier age and have more severe symptoms than do those with mutations in only one of the genes. Mutations in other genes may also be involved in early-onset glaucoma.

3.1. The Genes Associated with Early-onset Glaucoma

  • CYP1B1
  • MYOC

4. Inheritance

Early-onset glaucoma can have different inheritance patterns. Primary congenital glaucoma is usually inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.

Juvenile open-angle glaucoma is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some families, primary congenital glaucoma may also be inherited in an autosomal dominant pattern.

5. Other Names for This Condition

  • hereditary glaucoma

References

  1. Abu-Amero KK, Edward DP. Primary Congenital Glaucoma. 2004 Sep 30 [updated2017 Aug 17]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University ofWashington, Seattle; 1993-2020. Available fromhttp://www.ncbi.nlm.nih.gov/books/NBK1135/
  2. Achary MS, Reddy AB, Chakrabarti S, Panicker SG, Mandal AK, Ahmed N,Balasubramanian D, Hasnain SE, Nagarajaram HA. Disease-causing mutations inproteins: structural analysis of the CYP1B1 mutations causing primary congenital glaucoma in humans. Biophys J. 2006 Dec 15;91(12):4329-39.
  3. Acharya M, Mookherjee S, Bhattacharjee A, Bandyopadhyay AK, Daulat Thakur SK, Bhaduri G, Sen A, Ray K. Primary role of CYP1B1 in Indian juvenile-onset POAGpatients. Mol Vis. 2006 Apr 20;12:399-404.
  4. Bayat B, Yazdani S, Alavi A, Chiani M, Chitsazian F, Tusi BK, Suri F,Narooie-Nejhad M, Sanati MH, Elahi E. Contributions of MYOC and CYP1B1 mutations to JOAG. Mol Vis. 2008 Mar 13;14:508-17.
  5. Chakrabarti S, Kaur K, Rao KN, Mandal AK, Kaur I, Parikh RS, Thomas R. Thetranscription factor gene FOXC1 exhibits a limited role in primary congenitalglaucoma. Invest Ophthalmol Vis Sci. 2009 Jan;50(1):75-83. doi:10.1167/iovs.08-2253.
  6. Chavarria-Soley G, Sticht H, Aklillu E, Ingelman-Sundberg M, Pasutto F, ReisA, Rautenstrauss B. Mutations in CYP1B1 cause primary congenital glaucoma byreduction of either activity or abundance of the enzyme. Hum Mutat. 2008Sep;29(9):1147-53. doi: 10.1002/humu.20786.
  7. Chen Y, Jiang D, Yu L, Katz B, Zhang K, Wan B, Sun X. CYP1B1 and MYOCmutations in 116 Chinese patients with primary congenital glaucoma. ArchOphthalmol. 2008 Oct;126(10):1443-7. doi: 10.1001/archopht.126.10.1443.
  8. Choudhary D, Jansson I, Sarfarazi M, Schenkman JB. Characterization of thebiochemical and structural phenotypes of four CYP1B1 mutations observed inindividuals with primary congenital glaucoma. Pharmacogenet Genomics. 2008Aug;18(8):665-76. doi: 10.1097/FPC.0b013e3282ff5a36.
  9. Firasat S, Riazuddin SA, Khan SN, Riazuddin S. Novel CYP1B1 mutations inconsanguineous Pakistani families with primary congenital glaucoma. Mol Vis.2008;14:2002-9.
  10. Joe MK, Sohn S, Hur W, Moon Y, Choi YR, Kee C. Accumulation of mutantmyocilins in ER leads to ER stress and potential cytotoxicity in human trabecularmeshwork cells. Biochem Biophys Res Commun. 2003 Dec 19;312(3):592-600.
  11. Kaur K, Reddy AB, Mukhopadhyay A, Mandal AK, Hasnain SE, Ray K, Thomas R,Balasubramanian D, Chakrabarti S. Myocilin gene implicated in primary congenital glaucoma. Clin Genet. 2005 Apr;67(4):335-40.
  12. Ray K, Mukhopadhyay A, Acharya M. Recent advances in molecular genetics ofglaucoma. Mol Cell Biochem. 2003 Nov;253(1-2):223-31. Review.
  13. Turalba AV, Chen TC. Clinical and genetic characteristics of primaryjuvenile-onset open-angle glaucoma (JOAG). Semin Ophthalmol. 2008Jan-Feb;23(1):19-25. doi: 10.1080/08820530701745199. Review.
  14. Vasiliou V, Gonzalez FJ. Role of CYP1B1 in glaucoma. Annu Rev PharmacolToxicol. 2008;48:333-58. Review.
  15. Vincent AL, Billingsley G, Buys Y, Levin AV, Priston M, Trope G, Williams-Lyn D, Héon E. Digenic inheritance of early-onset glaucoma: CYP1B1, a potentialmodifier gene. Am J Hum Genet. 2002 Feb;70(2):448-60.
  16. Weisschuh N, Schiefer U. Progress in the genetics of glaucoma. Dev Ophthalmol.2003;37:83-93. Review.
  17. Wiggs JL, Lynch S, Ynagi G, Maselli M, Auguste J, Del Bono EA, Olson LM,Haines JL. A genomewide scan identifies novel early-onset primary open-angleglaucoma loci on 9q22 and 20p12. Am J Hum Genet. 2004 Jun;74(6):1314-20.
  18. Willoughby CE, Chan LL, Herd S, Billingsley G, Noordeh N, Levin AV, Buys Y,Trope G, Sarfarazi M, Héon E. Defining the pathogenicity of optineurin injuvenile open-angle glaucoma. Invest Ophthalmol Vis Sci. 2004 Sep;45(9):3122-30.
  19. WuDunn D. Genetic basis of glaucoma. Curr Opin Ophthalmol. 2002Apr;13(2):55-60. Review.
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Nicole Yin
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Update Date: 25 Dec 2020
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